1-nitroso-2-imidazolidone and process



United States Patent l-NITROSO-Z-IMIDAZOLIDONE AND PROCESS Julian G.Michels, Norwich, N. Y., assignor to The Norwich Pharmacal Company,Norwich, N. Y., a corporation of New York No Drawing. Application April5, 1956, Serial No. 57 6,236

2 Claims. (Cl. 260309.7)

This invention relates to a new method of preparingl-amino-Z-imidazolidone and to a new chemical compound which is usefulin carrying out my new method. My new compound isl-nitroso-Z-imidazolidone, described by the formula:

0 NN G 0 NH (3 Liz-06:

The compound l-amino-Z-imidazolidone is useful as an intermediate in thepreparation of N-(-nitro-2-furfurylidene)Lamino-Z-imidazolidone (seepending application Serial No. 511,435 filed May 26, 1955, and owned bythe assignee of this application).N-(5-nitro2-furfurylidene)-lamino-2-imidazolidone is a chemotherapeuticagent which is etfective in the treatment of animals lethally infectedwith representative species of both grarn negative and gram-positiveorganisms. For instance, when it is administered orally in sub-toxicamounts to animals infected with Salmonella typhosa. Salmonellacholeraesius or Streptococcus pyogertes organisms, n high order ofprotection is obtained.

The preparation of l-amino-Z-irnidazolidone was, prior to my invention,both cumbersome and expensive since it was necessary that a tediousmulti-step process be carried out. I have discovered that it is possibleto prepare 1- amino-2-imidazolidone in a much simpler and more directmanner and at a substantial saving over the prior process. The startingmaterial which I use in the practice of my new method isZ-imidazolidone, a comparatively inexpensive compound which is availablein plentiful supply.

l-amino-Z-imidazolidone is readily prepared according to my new methodby nitrosating Z-imidazolidone and then reducing the nitroso derivative.This can be done by dissolving the Z-irnidazolidone in a mineral acidsuch as hydrochloric acid and slowly adding thereto an alkaline nitritesuch as sodium nitrite at a temperature of about 05 C. This simpleprocedure produces my new compound, l-nitroso-2-imidazolidone, in goodyield as a readily handled precipitate which can be easily reduced togive the amino derivative. The reduction of my new compound can beeffected by known methods. The one which I now prefer, because of itssimplicity and low cost, is that involving the use of zinc dust indilute mineral acid solution.

In the preparation of the chemotherapeutic agent, N-(S-nitro-2-furfurylidene)-l-am-ino2-imidazolidone, from 1-amino-2-imidazolidone prepared according to my new method, thatintermediate need not be isolated from its solution. The addition tosaid solution of 5-nitro-2'fur- Patented Jan. 8, 1957 fural or areactive derivative thereof produces the desired end product inexcellent yield.

The preparation of my new compound, the steps which are followed in thepractice of my new method and the production ofN-(S-nitro-Z-furfurylidene)-l-amino-2- imidazolidone from the1-amino-2-imidazolidone prepared through my new method may be depictedschematically as follows:

in order that my invention may be fully available to those skilled inthe art, the following illustrative example is given:

Example To a solution of 4.2 g. (.05 mole) of Z-irnidazolidone in 50 cc.of 1 N hydrochloric acid, are added slowly with stirring at about 0 C.,3.5 g. (.05 mole) of sodium nitrite. When about of the nitrite has beenadded, a precipitate forms. After the remainder of the nitrite is added,the suspension is stirred for about one hour. This precipitate isfiltered and washed with cold water. There are obtained 3.6 g. (61%) ofcrystalline solid, l-nitroso-Z- imidazolidone, that melts withdecomposition at about C.

The 3.6 g. (.0313 mole) of 1-nitroso-2-imidazolidone are dissolved incc. of 10% hydrochloric acid and cooled to 2 C. To this solutionmaintained at about 10 C. are added in small portions 4.4 g. (.0673mole) of zinc dust. The temperature is allowed to rise to 20 C. and theexcess zinc is filtered. The addition of a solution of 4.5 g. (.032mole) of S-nitro-Z-furfural in alcohol to the clear colorless filtrate,results in the formation of an orange colored precipitate. This productis filtered, Washed with water, alcohol and ether and dried to give 4.75g. (68%) of N(5-nitr0-2-furfurylidene)-l-amino-2 imidazolidone whichmelts with decomposition at 253- 259 C. Recrystallization fromnitromethane using charcoal yields the pure compound melting withdecomposition at 261263 C.

What I claim is:

l. The method of preparing l-amino-Z-imidazolidone which comprisesnitrosating Z-imidazolidone by dissolving said 2-imidazolidone inhydrochloric acid and slowly adding sodium nitrite thereto at atemperature of about 0' to 5 C. to produce l-nitroso-2-imidazolidone,and then reducing said l-nitroso-2-imidazolidone by dissolving the samein dilute mineral acid and adding zinc dust thereto.

2. 1 nitroso 2 imidazolidone represented by the formula:

ONNO:O

Nu OllgUH No references cited.

1. THE METHOD OF PREPARING 1-AMINO-2-IMIDAZOLIDONE WHICH COMPRISES NITROSATING 2-IMIDAZOLIDONE BY DISSOLVING SAID 2-IMIDAZOLIDONE IN HYDROCHLORIC ACID AND SLOWLY ADDING SODIUM NITRITE THERETO AT A TEMPERATURE OF ABOUT 0* TO 5* C. TO PRODUCE 1-NITROSO-2-INIDAZOLIDONE, AND THEN REDUCING SAID 1-NITROSO-2-IMIDAZOLIDONE BY DISSOLVING THE SAME IN DILUTE MINERAL ACID AND ADDING ZINC DUST THERETO. 